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A yeast functional ...
A yeast functional screen predicts new candidate ALS disease genes
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Couthouis, Julien (author)
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Hart, Michael P (author)
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Shorter, James (author)
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DeJesus-Hernandez, Mariely (author)
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Erion, Renske (author)
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Oristano, Rachel (author)
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Liu, Annie X (author)
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Ramos, Daniel (author)
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Jethava, Niti (author)
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Hosangadi, Divya (author)
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Epstein, James (author)
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Chiang, Ashley (author)
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Diaz, Zamia (author)
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Nakaya, Tadashi (author)
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Ibrahim, Fadia (author)
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Kim, Hyung-Jun (author)
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Solski, Jennifer A (author)
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Williams, Kelly L (author)
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Mojsilovic-Petrovic, Jelena (author)
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- Ingre, Caroline (author)
- Karolinska Institutet,Umeå universitet,Neurologi
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Boylan, Kevin (author)
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Graff-Radford, Neill R (author)
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Dickson, Dennis W (author)
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Clay-Falcone, Dana (author)
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Elman, Lauren (author)
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McCluskey, Leo (author)
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Greene, Robert (author)
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Kalb, Robert G (author)
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Lee, Virginia M-Y (author)
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Trojanowski, John Q (author)
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Ludolph, Albert (author)
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Robberecht, Wim (author)
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- Andersen, Peter M (author)
- Umeå universitet,Neurologi
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Nicholson, Garth A (author)
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Blair, Ian P (author)
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King, Oliver D (author)
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Bonini, Nancy M (author)
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Van Deerlin, Vivianna (author)
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Rademakers, Rosa (author)
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Mourelatos, Zissimos (author)
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Gitler, Aaron D (author)
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(creator_code:org_t)
- 2011-11-07
- 2011
- English.
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 108:52, s. 20881-20890
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Amyotrophic lateral sclerosis (ALS) is a devastating and universally fatal neurodegenerative disease. Mutations in two related RNA-binding proteins, TDP-43 and FUS, that harbor prion-like domains, cause some forms of ALS. There are at least 213 human proteins harboring RNA recognition motifs, including FUS and TDP-43, raising the possibility that additional RNA-binding proteins might contribute to ALS pathogenesis. We performed a systematic survey of these proteins to find additional candidates similar to TDP-43 and FUS, followed by bioinformatics to predict prion-like domains in a subset of them. We sequenced one of the segenes, TAF15, in patients with ALS and identified missense variants, which were absent in a large number of healthy controls. These disease-associated variants of TAF15 caused formation of cytoplasmic foci when expressed in primary cultures of spinal cord neurons. Very similar to TDP-43 and FUS, TAF15 aggregated in vitro and conferred neurodegeneration in Drosophila, with the ALS-linked variants having amore severe effect than wild type. Immunohistochemistry of postmortem spinal cord tissue revealed mislocalization of TAF15 in motor neurons of patients with ALS. We propose that aggregation-prone RNA-binding proteins might contribute very broadly to ALS pathogenesis and the genes identified in our yeast functional screen, coupled with prion-like domain prediction analysis, now provide a powerful resource to facilitate ALS disease gene discovery.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- amyotrophic-lateral-sclerosis; frontotemporal lobar degeneration; drosophila model; fus mutations; tdp-43 proteinopathy; amyloid pores; wild-type; toxicity; neurodegeneration; aggregation
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Couthouis, Julie ...
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Hart, Michael P
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Shorter, James
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DeJesus-Hernande ...
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Erion, Renske
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Oristano, Rachel
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show more...
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Liu, Annie X
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Ramos, Daniel
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Jethava, Niti
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Hosangadi, Divya
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Epstein, James
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Chiang, Ashley
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Diaz, Zamia
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Nakaya, Tadashi
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Ibrahim, Fadia
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Kim, Hyung-Jun
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Solski, Jennifer ...
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Williams, Kelly ...
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Mojsilovic-Petro ...
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Ingre, Caroline
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Boylan, Kevin
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Graff-Radford, N ...
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Dickson, Dennis ...
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Clay-Falcone, Da ...
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Elman, Lauren
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McCluskey, Leo
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Greene, Robert
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Kalb, Robert G
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Lee, Virginia M- ...
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Trojanowski, Joh ...
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Ludolph, Albert
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Robberecht, Wim
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Andersen, Peter ...
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Nicholson, Garth ...
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Blair, Ian P
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King, Oliver D
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Bonini, Nancy M
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Van Deerlin, Viv ...
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Rademakers, Rosa
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Mourelatos, Ziss ...
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Gitler, Aaron D
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Proceedings of t ...
- By the university
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Umeå University
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Karolinska Institutet